Machine learning in medicine: Performance calculation of dementia prediction by support vector machines (SVM)

Machine Learning (ML) is considered as one of the contemporary approaches in predicting, identifying, and making decisions without having human involvement. ML is quickly evolving in the medical industry ranging from diagnosis to visualization of diseases and the study of disease transmission. These algorithms were developed to identify the problems in medical image processing. Numerous studies previously attempted to apply these algorithms on MRI (Magnetic Resonance Image) data to predict AD (Alzheimer's disease) in advance. The present study aims to explore the usage of support vector machine (SVM) in the prediction of dementia and validate its performance through statistical analysis. Data is obtained from the Open Access Series of Imaging Studies (OASIS-2) longitudinal collection of 150 subjects of 373 MRI data. Results provide evidence that better performance values for dementia prediction are achieved by low gamma (1.0E-4) and high regularized (C = 100) values. The proposed approach is shown to achieve accuracy and precision of 68.75% and 64.18%. Keywords: Machine learning, OASIS, Support vector machines, Kernel, Gamma, Regularization (C

Predicting Alzheimer’s disease progression using multi-modal deep learning approach

Alzheimer’s disease (AD) is a progressive neurodegenerative condition marked by a decline in cognitive functions with no validated disease modifying treatment. It is critical for timely treatment to detect AD in its earlier stage before clinical manifestation. Mild cognitive impairment (MCI) is an intermediate stage between cognitively normal older adults and AD. To predict conversion from MCI to probable AD, we applied a deep learning approach, multimodal recurrent neural network. We developed an integrative framework that combines not only cross-sectional neuroimaging biomarkers at baseline but also longitudinal cerebrospinal fluid (CSF) and cognitive performance biomarkers obtained from the Alzheimer’s Disease Neuroimaging Initiative cohort (ADNI). The proposed framework integrated longitudinal multi-domain data. Our results showed that 1) our prediction model for MCI conversion to AD yielded up to 75% accuracy (area under the curve (AUC) = 0.83) when using only single modality of data separately; and 2) our prediction model achieved the best performance with 81% accuracy (AUC = 0.86) when incorporating longitudinal multi-domain data. A multi-modal deep learning approach has potential to identify persons at risk of developing AD who might benefit most from a clinical trial or as a stratification approach within clinical trials

Temporally Constrained Group Sparse Learning for Longitudinal Data Analysis in Alzheimer's Disease

Sparse learning has been widely investigated for analysis of brain images to assist the diagnosis of Alzheimer’s disease (AD) and its prodromal stage, i.e., mild cognitive impairment (MCI). However, most existing sparse learning-based studies only adopt cross-sectional analysis methods, where the sparse model is learned using data from a single time-point. Actually, multiple time-points of data are often available in brain imaging applications, which can be used in some longitudinal analysis methods to better uncover the disease progression patterns. Accordingly, in this paper we propose a novel temporally-constrained group sparse learning method aiming for longitudinal analysis with multiple time-points of data. Specifically, we learn a sparse linear regression model by using the imaging data from multiple time-points, where a group regularization term is first employed to group the weights for the same brain region across different time-points together. Furthermore, to reflect the smooth changes between data derived from adjacent time-points, we incorporate two smoothness regularization terms into the objective function, i.e., one fused smoothness term which requires that the differences between two successive weight vectors from adjacent time-points should be small, and another output smoothness term which requires the differences between outputs of two successive models from adjacent time-points should also be small. We develop an efficient optimization algorithm to solve the proposed objective function. Experimental results on ADNI database demonstrate that, compared with conventional sparse learning-based methods, our proposed method can achieve improved regression performance and also help in discovering disease-related biomarkers

Machine Learning for Multiclass Classification and Prediction of Alzheimer\u27s Disease

Alzheimer\u27s disease (AD) is an irreversible neurodegenerative disorder and a common form of dementia. This research aims to develop machine learning algorithms that diagnose and predict the progression of AD from multimodal heterogonous biomarkers with a focus placed on the early diagnosis. To meet this goal, several machine learning-based methods with their unique characteristics for feature extraction and automated classification, prediction, and visualization have been developed to discern subtle progression trends and predict the trajectory of disease progression. The methodology envisioned aims to enhance both the multiclass classification accuracy and prediction outcomes by effectively modeling the interplay between the multimodal biomarkers, handle the missing data challenge, and adequately extract all the relevant features that will be fed into the machine learning framework, all in order to understand the subtle changes that happen in the different stages of the disease. This research will also investigate the notion of multitasking to discover how the two processes of multiclass classification and prediction relate to one another in terms of the features they share and whether they could learn from one another for optimizing multiclass classification and prediction accuracy. This research work also delves into predicting cognitive scores of specific tests over time, using multimodal longitudinal data. The intent is to augment our prospects for analyzing the interplay between the different multimodal features used in the input space to the predicted cognitive scores. Moreover, the power of modality fusion, kernelization, and tensorization have also been investigated to efficiently extract important features hidden in the lower-dimensional feature space without being distracted by those deemed as irrelevant. With the adage that a picture is worth a thousand words, this dissertation introduces a unique color-coded visualization system with a fully integrated machine learning model for the enhanced diagnosis and prognosis of Alzheimer\u27s disease. The incentive here is to show that through visualization, the challenges imposed by both the variability and interrelatedness of the multimodal features could be overcome. Ultimately, this form of visualization via machine learning informs on the challenges faced with multiclass classification and adds insight into the decision-making process for a diagnosis and prognosis

Prediction of Alzheimer's disease dementia with MRI beyond the short-term: Implications for the design of predictive models

Magnetic resonance imaging (MRI) volumetric measures have become a standard tool for the detection of in-cipientAlzheimer'sDisease(AD)dementiainmildcognitiveimpairment(MCI).Focusedonprovidinganearlierand more accurate diagnosis, sophisticated MRI machine learning algorithms have been developed over therecentyears,mostofthemlearningtheirnon-diseasepatternsfromMCIthatremainedstableover2–3years.Inthis work, we analyzed whether these stable MCI over short-term periods are actually appropriate trainingexamples of non-disease patterns. To this aim, we compared the diagnosis of MCI patients at 2 and 5years offollow-up and investigated its impact on the predictive performance of baseline volumetric MRI measures pri-marily involved in AD, i.e., hippocampal and entorhinal cortex volumes. Predictive power was evaluated interms ofthe areaunder the ROCcurve(AUC), sensitivity,andspecificity inatrialsample of248 MCIpatientsfollowed-up over 5years. We further compared the sensitivity in those MCI that converted before 2years andthose that converted after 2years. Our results indicate that 23% of the stable MCI at 2years progressed in thenextthreeyearsandthatMRIvolumetricmeasuresaregoodpredictorsofconversiontoADdementiaevenatthemid-term, showing a better specificity and AUC as follow-up time increases. The combination of hippocampusand entorhinal cortex yielded an AUC that was significantly higher for the 5-year follow-up (AUC=73% at2yearsvs.AUC=84%at5years),aswellasforspecificity(56%vs.71%).Sensitivityshowedanon-significantslightdecrease(81%vs.78%).Remarkably,theperformanceofthismodelwascomparabletomachinelearningmodels at the same follow-up times. MRI correctly identified most of the patients that converted after 2years(with sensitivity>60%), and these patients showed a similar degree of abnormalities to those that convertedbefore 2years. This implies that most of the MCI patients that remained stable over short periods and subse-quentlyprogressedtoADdementiahadevidentatrophiesatbaseline.Therefore,machinelearningmodelsthatuse these patients to learn non-disease patterns are including an important fraction of patients with evidentpathological changes related to the disease, something that might result in reduced performance and lack ofbiological interpretability.This work was partially supported by the project PI16/01416(ISCIIIco-fundedFEDER) and RYC-2015/17430 (RamónyCajal,Pablo Aguiar). Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI)(National Institutes of Health Grant U01AG024904) and DODADNI (Department of Defense award number W81XWH-12-2-0012)S

Abordagem CNN 2D estendida para o diagnóstico da doença de Alzheimer através de imagens de ressonância magnética estrutural

Orientadores: Leticia Rittner, Roberto de Alencar LotufoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Elétrica e de ComputaçãoResumo: A doença de Alzheimer (AD - Alzheimer's disease) é um tipo de demência que afeta milhões de pessoas em todo o mundo. Até o momento, não há cura para a doença e seu diagnóstico precoce tem sido uma tarefa desafiadora. As técnicas atuais para o seu diagnóstico têm explorado as informações estruturais da Imagem por Ressonância Magnética (MRI - Magnetic Resonance Imaging) em imagens ponderadas em T1. Entre essas técnicas, a rede neural convolucional (CNN - Convolutional Neural Network) é a mais promissora e tem sido usada com sucesso em imagens médicas para uma variedade de aplicações devido à sua capacidade de extração de características. Antes do grande sucesso do aprendizado profundo e das CNNs, os trabalhos que objetivavam classificar os diferentes estágios de AD exploraram abordagens clássicas de aprendizado de máquina e uma meticulosa extração de características, principalmente para classificar testes binários. Recentemente, alguns autores combinaram técnicas de aprendizagem profunda e pequenos subconjuntos do conjunto de dados públicos da Iniciativa de Neuroimagem da Doença de Alzheimer (ADNI - Alzheimer's Disease Neuroimaging Initiative) para prever um estágio inicial da doença explorando abordagens 3D CNN geralmente combinadas com arquiteturas de auto-codificador convolucional 3D. Outros também exploraram uma abordagem de CNN 3D combinando-a ou não com uma etapa de pré-processamento para a extração de características. No entanto, a maioria desses trabalhos focam apenas na classificação binária, sem resultados para AD, comprometimento cognitivo leve (MCI - Mild Cognitive Impairment) e classificação de sujeitos normais (NC - Normal Control). Nosso principal objetivo foi explorar abordagens de CNN 2D para a tarefa de classificação das 3 classes usando imagens de MRI ponderadas em T1. Como objetivo secundário, preenchemos algumas lacunas encontradas na literatura ao investigar o uso de arquiteturas CNN 2D para o nosso problema, uma vez que a maioria dos trabalhos explorou o aprendizado de máquina clássico ou abordagens CNN 3D. Nossa abordagem CNN 2D estendida explora as informações volumétricas dos dados de ressonância magnética, mantendo baixo custo computacional associado a uma abordagem 2D, quando comparados às abordagens 3D. Além disso, nosso resultado supera as outras estratégias para a classificação das 3 classes e comparando o desempenho de nosso modelo com os métodos tradicionais de aprendizado de máquina e 3D CNN. Também investigamos o papel de diferentes técnicas amplamente utilizadas em aplicações CNN, por exemplo, pré-processamento de dados, aumento de dados, transferência de aprendizado e adaptação de domínio para um conjunto de dados brasileiroAbstract: Alzheimer's disease (AD) is a type of dementia that affects millions of people around the world. To date, there is no cure for Alzheimer's and its early-diagnosis has been a challenging task. The current techniques for Alzheimer's disease diagnosis have explored the structural information of Magnetic Resonance Imaging (MRI) in T1-weighted images. Among these techniques, deep convolutional neural network (CNN) is the most promising one and has been successfully used in medical images for a variety of applications due to its ability to perform features extraction. Before the great success of deep learning and CNNs, the works that aimed to classify the different stages of AD explored classic machine learning approaches and a meticulous feature engineering extraction, mostly to classify binary tasks. Recently, some authors have combined deep learning techniques and small subsets from the Alzheimer's Disease Neuroimaging Initiative (ADNI) public dataset, to predict an early-stage of AD exploring 3D CNN approaches usually combined with 3D convolutional autoencoder architectures. Others have also investigated a 3D CNN approach combining it or not with a pre-processing step for the extraction of features. However, the majority of these papers focus on binary classification only, with no results for Alzheimer's disease, Mild Cognitive Impairment (MCI), and Normal Control (NC) classification. Our primary goal was to explore 2D CNN approaches to tackle the 3-class classification using T1-weighted MRI. As a secondary goal, we filled some gaps we found in the literature by investigating the use of 2D CNN architectures to our problem, since most of the works either explored traditional machine learning or 3D CNN approaches. Our extended-2D CNN explores the MRI volumetric data information while maintaining the low computational costs associated with a 2D approach when compared to 3D-CNNs. Besides, our result overcomes the other strategies for the 3-class classification while analyzing the performance of our model with traditional machine-learning and 3D-CNN methods. We also investigated the role of different widely used techniques in CNN applications, for instance, data pre-processing, data augmentation, transfer-learning, and domain-adaptation to a Brazilian datasetMestradoEngenharia de ComputaçãoMestra em Engenharia Elétrica168468/2017-4  CNP

Predictive analytics applied to Alzheimer’s disease : a data visualisation framework for understanding current research and future challenges

Dissertation as a partial requirement for obtaining a master’s degree in information management, with a specialisation in Business Intelligence and Knowledge Management.Big Data is, nowadays, regarded as a tool for improving the healthcare sector in many areas, such as in its economic side, by trying to search for operational efficiency gaps, and in personalised treatment, by selecting the best drug for the patient, for instance. Data science can play a key role in identifying diseases in an early stage, or even when there are no signs of it, track its progress, quickly identify the efficacy of treatments and suggest alternative ones. Therefore, the prevention side of healthcare can be enhanced with the usage of state-of-the-art predictive big data analytics and machine learning methods, integrating the available, complex, heterogeneous, yet sparse, data from multiple sources, towards a better disease and pathology patterns identification. It can be applied for the diagnostic challenging neurodegenerative disorders; the identification of the patterns that trigger those disorders can make possible to identify more risk factors, biomarkers, in every human being. With that, we can improve the effectiveness of the medical interventions, helping people to stay healthy and active for a longer period. In this work, a review of the state of science about predictive big data analytics is done, concerning its application to Alzheimer’s Disease early diagnosis. It is done by searching and summarising the scientific articles published in respectable online sources, putting together all the information that is spread out in the world wide web, with the goal of enhancing knowledge management and collaboration practices about the topic. Furthermore, an interactive data visualisation tool to better manage and identify the scientific articles is develop, delivering, in this way, a holistic visual overview of the developments done in the important field of Alzheimer’s Disease diagnosis.Big Data é hoje considerada uma ferramenta para melhorar o sector da saúde em muitas áreas, tais como na sua vertente mais económica, tentando encontrar lacunas de eficiência operacional, e no tratamento personalizado, selecionando o melhor medicamento para o paciente, por exemplo. A ciência de dados pode desempenhar um papel fundamental na identificação de doenças em um estágio inicial, ou mesmo quando não há sinais dela, acompanhar o seu progresso, identificar rapidamente a eficácia dos tratamentos indicados ao paciente e sugerir alternativas. Portanto, o lado preventivo dos cuidados de saúde pode ser bastante melhorado com o uso de métodos avançados de análise preditiva com big data e de machine learning, integrando os dados disponíveis, geralmente complexos, heterogéneos e esparsos provenientes de múltiplas fontes, para uma melhor identificação de padrões patológicos e da doença. Estes métodos podem ser aplicados nas doenças neurodegenerativas que ainda são um grande desafio no seu diagnóstico; a identificação dos padrões que desencadeiam esses distúrbios pode possibilitar a identificação de mais fatores de risco, biomarcadores, em todo e qualquer ser humano. Com isso, podemos melhorar a eficácia das intervenções médicas, ajudando as pessoas a permanecerem saudáveis e ativas por um período mais longo. Neste trabalho, é feita uma revisão do estado da arte sobre a análise preditiva com big data, no que diz respeito à sua aplicação ao diagnóstico precoce da Doença de Alzheimer. Isto foi realizado através da pesquisa exaustiva e resumo de um grande número de artigos científicos publicados em fontes online de referência na área, reunindo a informação que está amplamente espalhada na world wide web, com o objetivo de aprimorar a gestão do conhecimento e as práticas de colaboração sobre o tema. Além disso, uma ferramenta interativa de visualização de dados para melhor gerir e identificar os artigos científicos foi desenvolvida, fornecendo, desta forma, uma visão holística dos avanços científico feitos no importante campo do diagnóstico da Doença de Alzheimer

3D shape matching and registration : a probabilistic perspective

Dense correspondence is a key area in computer vision and medical image analysis. It has applications in registration and shape analysis. In this thesis, we develop a technique to recover dense correspondences between the surfaces of neuroanatomical objects over heterogeneous populations of individuals. We recover dense correspondences based on 3D shape matching. In this thesis, the 3D shape matching problem is formulated under the framework of Markov Random Fields (MRFs). We represent the surfaces of neuroanatomical objects as genus zero voxel-based meshes. The surface meshes are projected into a Markov random field space. The projection carries both geometric and topological information in terms of Gaussian curvature and mesh neighbourhood from the original space to the random field space. Gaussian curvature is projected to the nodes of the MRF, and the mesh neighbourhood structure is projected to the edges. 3D shape matching between two surface meshes is then performed by solving an energy function minimisation problem formulated with MRFs. The outcome of the 3D shape matching is dense point-to-point correspondences. However, the minimisation of the energy function is NP hard. In this thesis, we use belief propagation to perform the probabilistic inference for 3D shape matching. A sparse update loopy belief propagation algorithm adapted to the 3D shape matching is proposed to obtain an approximate global solution for the 3D shape matching problem. The sparse update loopy belief propagation algorithm demonstrates significant efficiency gain compared to standard belief propagation. The computational complexity and convergence property analysis for the sparse update loopy belief propagation algorithm are also conducted in the thesis. We also investigate randomised algorithms to minimise the energy function. In order to enhance the shape matching rate and increase the inlier support set, we propose a novel clamping technique. The clamping technique is realized by combining the loopy belief propagation message updating rule with the feedback from 3D rigid body registration. By using this clamping technique, the correct shape matching rate is increased significantly. Finally, we investigate 3D shape registration techniques based on the 3D shape matching result. Based on the point-to-point dense correspondences obtained from the 3D shape matching, a three-point based transformation estimation technique is combined with the RANdom SAmple Consensus (RANSAC) algorithm to obtain the inlier support set. The global registration approach is purely dependent on point-wise correspondences between two meshed surfaces. It has the advantage that the need for orientation initialisation is eliminated and that all shapes of spherical topology. The comparison of our MRF based 3D registration approach with a state-of-the-art registration algorithm, the first order ellipsoid template, is conducted in the experiments. These show dense correspondence for pairs of hippocampi from two different data sets, each of around 20 60+ year old healthy individuals

Deep Interpretability Methods for Neuroimaging

Brain dynamics are highly complex and yet hold the key to understanding brain function and dysfunction. The dynamics captured by resting-state functional magnetic resonance imaging data are noisy, high-dimensional, and not readily interpretable. The typical approach of reducing this data to low-dimensional features and focusing on the most predictive features comes with strong assumptions and can miss essential aspects of the underlying dynamics. In contrast, introspection of discriminatively trained deep learning models may uncover disorder-relevant elements of the signal at the level of individual time points and spatial locations. Nevertheless, the difficulty of reliable training on high-dimensional but small-sample datasets and the unclear relevance of the resulting predictive markers prevent the widespread use of deep learning in functional neuroimaging. In this dissertation, we address these challenges by proposing a deep learning framework to learn from high-dimensional dynamical data while maintaining stable, ecologically valid interpretations. The developed model is pre-trainable and alleviates the need to collect an enormous amount of neuroimaging samples to achieve optimal training. We also provide a quantitative validation module, Retain and Retrain (RAR), that can objectively verify the higher predictability of the dynamics learned by the model. Results successfully demonstrate that the proposed framework enables learning the fMRI dynamics directly from small data and capturing compact, stable interpretations of features predictive of function and dysfunction. We also comprehensively reviewed deep interpretability literature in the neuroimaging domain. Our analysis reveals the ongoing trend of interpretability practices in neuroimaging studies and identifies the gaps that should be addressed for effective human-machine collaboration in this domain. This dissertation also proposed a post hoc interpretability method, Geometrically Guided Integrated Gradients (GGIG), that leverages geometric properties of the functional space as learned by a deep learning model. With extensive experiments and quantitative validation on MNIST and ImageNet datasets, we demonstrate that GGIG outperforms integrated gradients (IG), which is considered to be a popular interpretability method in the literature. As GGIG is able to identify the contours of the discriminative regions in the input space, GGIG may be useful in various medical imaging tasks where fine-grained localization as an explanation is beneficial